Researchers at the University of Michigan have identified a new potential therapeutic target for lowering cholesterol that could be an alternative or complementary therapy to statins.
Scientists in the lab of David Ginsburg at the Life Sciences Institute inhibited the action of a gene responsible for transporting a protein that interferes with the ability of the liver to remove cholesterol from the blood in mice. Trapping the destructive protein where it couldn’t harm receptors responsible for removing cholesterol preserved the liver cells’ capacity to clear plasma cholesterol from the blood, but did not appear to otherwise affect the health of the mice.
In the research, published April 9 in the online journal eLife, scientists found that mice with an inactive SEC24A gene could develop normally. However, their plasma cholesterol levels were reduced by 45 percent because vesicles from liver cells were not able to recruit and transport a critical regulator of blood cholesterol levels called proprotein convertase subtilisin/kexin type 9. PCSK9 is a secretory protein that destroys the liver cells’ receptors of low-density lipoprotein- LDL, the so-called “bad cholesterol”-and prevents the cells from removing the LDL.
“Inhibiting SEC24A or PCSK9 may be an alternative to statins, and could work together with statins to produce even greater effects,” said Xiao-Wei Chen of the Ginsburg lab, the first author on the paper. “Also, they might be effective on patients who are resistant to or intolerant of statins.”
Initial studies of anti-PCSK9 therapies in humans have shown that eliminating PCSK9 can lower cholesterol dramatically and work with statins like Lipitor to lower it even further. The Ginsburg lab’s research points to a new area for study: rather than inhibiting PCSK9 itself, perhaps future therapies could block the transport mechanism that allows the destructive protein to reach the LDL receptors.
The paper, “SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion,” explains the mechanism by which cells transport PCSK9. Vesicles transport proteins in the cell; the Ginsburg lab’s research focused on a specialized type of vesicle packaged by the Coat Protein Complex II, which regulates the metabolism of cholesterol, among many other things. These vesicles selectively transport cargo proteins including PCSK9.
Got High cholesterol? Learn what you can do to lower it quickly - starting today.
Read Beyond “Low-Fat”
Even foods that claim to be “low-fat” may contribute significantly to fat intake if you eat more than one serving. The label phrase “low-fat” means the product contains 3 grams or less per serving. Be sure to check the serving size on the nutrition facts label and account for the extra fat (and calories) consumed if you eat more than one serving.
Research suggests that increasing soluble fiber intake by 5 to 10 grams each day may result in a 5 percent drop in LDL cholesterol. Start the day with a cup of oatmeal, put a ½ cup of beans on your salad at lunch, eat broccoli with dinner and snack on an orange or a pear and you’ll easily meet the target range.
Eat Eggs, In Moderation
Eggs are no longer on the cholesterol blacklist. The daily recommended cholesterol limit is 300 milligrams of cholesterol and one egg contains about 213. So if you’re going to eat an egg in the morning, simply limit how much cholesterol you get that day from other sources. Substitute some veggies for meat at dinner, or skip the half-and-half in your coffee.
Start The Day Right
Choose hot or cold breakfast cereals, such as oatmeal and oat bran, that have about 2 grams of soluble fiber and 4 to 6 grams of total fiber per 1-cup serving. Add a banana or other fruit to boost fiber even more. This will help keep LDL cholesterol low.
Avoid Double Cholesterol Whammy
Dietary cholesterol can elevate your blood cholesterol levels, but saturated fat has an even worse effect. However, the two are often found in the same foods, including meat, butter and full-fat dairy. So by limiting your intake of foods rich in saturated fat, you’ll also help reduce your intake of cholesterol.
Know Your Sources Of Trans Fat
Since 2006, the FDA has required food manufacturers to list reportable amounts of trans fat on the nutrition facts label. What’s considered reportable? Food manufacturers don’t have to report the trans-fat content if it’s less than 0.5 gram per serving. So check the ingredients list for hydrogenated or partially hydrogenated vegetable oils even if the nutrition facts label reports 0 grams of trans fat.
Twice a week, substitute a fatty fish, such as salmon or tuna, for a higher-fat meat like beef. These fish are rich in omega-3s, a type of polyunsaturated fat, that may help lower your blood cholesterol level when substituted for saturated and trans fats in your diet.
Without those LDL receptors (LDLR), liver cells are not able to remove LDLs from the bloodstream, so protecting the LDLR from PCSK9 would allow the receptors to continue to remove cholesterol.
Walnuts, almonds and other nuts
Walnuts, almonds and other nuts can reduce blood cholesterol. Rich in polyunsaturated fatty acids, walnuts also help keep blood vessels healthy.
Eating about a handful (1.5 ounces, or 42.5 grams) a day of most nuts, such as almonds, hazelnuts, peanuts, pecans, some pine nuts, pistachio nuts and walnuts, may reduce your risk of heart disease. Just make sure the nuts you eat aren’t salted or coated with sugar.
All nuts are high in calories, so a handful will do. To avoid eating too many nuts and gaining weight, replace foods high in saturated fat with nuts. For example, instead of using cheese, meat or croutons in your salad, add a handful of walnuts or almonds.
“Without SEC24A, much of the PCSK9 couldn’t make its way out of the cells to destroy the LDLR, which then clears cholesterol from the blood,” Chen said.
The part of the vesicle that selects which proteins to transport is SEC24. By blocking SEC24A gene, the researchers disabled the vesicle’s selection of PCSK9. The destructive protein remained trapped within the cells, leaving the LDLR intact and enabling the liver to clear the body of cholesterol that otherwise could accumulate in arteries.